Cancer is characterized primarily by an increase in the number of abnormal cells derived from a given normal tissue, invasion of adjacent tissues by the abnormal cells, or lymphatic or blood-borne spread of malignant cells to regional lymph nodes and to distant sites (metastasis). Clinical data and molecular biologic studies indicate that cancer is a multistep process that begins with minor pre-neoplastic changes, which may under certain conditions progress to neoplasia.
Primary liver cancer is one of the most common forms of cancer in the world. There are two main types of liver cancer: hepatocellular carcinoma (HCC), also known as malignant hepatoma, and cholangiocellular carcinoma. HCC is the most common form of primary liver cancer, and develops within the hepatocyte. HCC occurs mostly in men and patients that suffer from cirrhosis. In contrast, cholangiocellular carcinoma or bile duct cancer develops in the small bile ducts within the liver. This type of cancer is more common among women. HCC is the one of the most common cancers worldwide and the third most common cause of cancer-related deaths. The disease is often diagnosed late in the course of clinical manifestation. As a result, only 10-15% of patients are candidates for curative surgery. For the majority of HCC patients, systemic chemotherapies or supportive therapies are the mainstay treatment options.
Up to the present time, there are a limited number of drugs that can effectively treat cancer such as HCC. For example, patients with metastatic hepatocellular carcinoma or hepatocellular carcinoma, where local treatment has failed, normally survive for only three to four months. Metastatic hepatocellular carcinoma or hepatocellular carcinoma, where local treatment has failed, is mainly subjected to systemic therapy. The use of doxorubicin, a high dosage of tamoxifen in combination doxorubicin or EA-PFL (etoposide, adriamycin, cisplatin, fluorouracil and leucovorin), is an effective example. The remission rate of these drugs can achieve levels between 15 and 30%. However, because the patients of hepatocellular carcinoma usually develop complication of liver cirrhosis and other complications (such as leukopenia, thrombopenia or liver function impairment), they cannot be subject to systemic chemotherapy. Further, most chemotherapeutic agents show limited effectiveness and have not been able to significantly improve patient survival. Despite ongoing efforts, the adverse clinical course of most cancer patients underscores the needs for more efficacious chemotherapies.
The present invention addresses these needs. Therefore, it is the object of the present invention to provide improved methods of treating or preventing cancer such as hepatocellular carcinoma.